Microdialysis is widely used in animal models and human patients to monitor and assess the extracellular neurochemistry of the living, intact brain. It has made significant contributions to the study of the neurochemistry of behavior, CNS pathology, drug discovery, and clinical care. Despite its many beneficial attributes, microdialysis suffers from an overlooked drawback in that implanting the probes causes a penetration injury to the tissues being analyzed. The penetration injury results in opening of the blood brain barrier, ischemia of the tissue surrounding the probe, and the activation of astrocytes that eventually engulf the probe track in a glial scar. The penetration injury affects the outcome of microdialysis experiments, i.e. the results reflect the neurochemical attributes of the injured, rather than normal, tissues. The goal of the research proposed here is to establish the feasibility of ameliorating the penetration injury and its impact on microdialysis results by the combined use of a powerful anti-inflammatory drug, dexamethasone, and a novel mitochondrially-targeted electron and radical scavenging cytoprotective agent. The outcome of this research will have a lasting and significant impact on the several branches of neuroscience that involve the insertion of devices into brain tissues, including microdialysis, electrochemical sensors, and neuroprosthetic devices such as deep brain stimulators and neuron recordings arrays.